Preparation method of 3-bromohydrazinobenzene hydrochloride

Abstract

The invention relates to a preparation method of 3-bromohydrazinobenzene hydrochloride, which comprises the steps of diazotization, reduction, purification and salification. In the diazotization and reduction steps, concentrated hydrochloric acid is adopted to keep the reaction solution strongly acidic, thereby ensuring the smooth performance of the reaction. In the reduction step, the zinc powder-concentrated hydrochloric acid is used as the reducer instead of sodium thiosulfate, sodium bisulfite, stannous chloride-hydrochloric acid or the like, and thus, has the advantages of favorable reducibility, high yield and shorter reaction time; and zinc hydroxide and other impurities generated in the reaction are convenient to remove, and thus, the product has fewer impurities and higher purity. In the salification step, acetone is used for rinsing, thereby enhancing the purity of the product and ensuring the appearance of the product. The preparation method is stable and reliable in technique and easy to operate; the product purity is high (the content by high performance liquid chromatography is at least 99%), and the yield is at least 38%; and thus, the invention completely satisfies the demands of the market for 3-bromohydrazinobenzene hydrochloride.

Description

technical field

[0001] The invention relates to the technical field of preparation of organic compounds, in particular to a preparation method of 3-bromophenylhydrazine hydrochloride. Background technique

[0002] As an important organic synthesis intermediate, 3-bromophenylhydrazine hydrochloride is widely used in the pharmaceutical manufacturing industry and has a broad market prospect. And the product obtained by the preparation method of existing 3-bromophenylhydrazine hydrochloride has high impurity content, low purity, poor stability and small output, which cannot meet the needs of the market. Contents of the invention

[0003] The purpose of the invention is to overcome the deficiencies in the prior art, and provide a preparation method of 3-bromophenylhydrazine hydrochloride with high purity, large output and good stability.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A preparation method...

Examples

Embodiment 1

[0018] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0019] ⑴ diazotization

[0020] Add 50g of 3-bromoaniline and 150ml of 37% concentrated hydrochloric acid into a 1L three-necked flask, cool to 2°C with ice salt, add 65g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1 hour.

[0021] ⑵ reduction

[0022] Add 450ml of 37% concentrated hydrochloric acid, 450ml of water and 120g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 20% sodium hydroxide solution until the pH value of the reaction solution is 10, After 1 hour of heat preservation at 5°C, crystals were precipitated, and 24 g of crude 3-bromophenylhydrazine was obtained by filtration.

[0023] ⑶ Purification

[0024] Dissolve 24g of crude 3-bromophenylhydrazine in 480g of water, heat to 60°C to dissolve it completely, the...

Embodiment 2

[0028] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0029] ⑴ diazotization

[0030] Add 200g of 3-bromoaniline and 600ml of 37% concentrated hydrochloric acid into a 5L three-necked flask, cool to 2°C with ice salt, add 270g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0031] ⑵ reduction

[0032] Add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 195g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 25% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 1.5 hours, crystals were precipitated, and 115g of crude 3-bromophenylhydrazine was obtained by filtration.

[0033] ⑶ Purification

[0034] Dissolve 115g of crude 3-bromophenylhydrazine in 2300g of water, heat to 60°C to dissolve it completely, then add a...

Embodiment 3

[0038] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0039] ⑴ diazotization

[0040] Add 500g of 3-bromoaniline and 1500ml of 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 650g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0041] ⑵ reduction

[0042] Add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 480g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 30% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 2 hours, crystals were precipitated, and 269g of crude 3-bromophenylhydrazine was obtained by filtration.

[0043] ⑶ Purification

[0044] Dissolve 269g of crude 3-bromophenylhydrazine in 5380g of water, heat to 60°C to dissolve it completely, add an app...

technical field

[0001] The invention relates to the technical field of preparation of organic compounds, in particular to a preparation method of 3-bromophenylhydrazine hydrochloride. Background technique

[0002] As an important organic synthesis intermediate, 3-bromophenylhydrazine hydrochloride is widely used in the pharmaceutical manufacturing industry and has a broad market prospect. And the product obtained by the preparation method of existing 3-bromophenylhydrazine hydrochloride has high impurity content, low purity, poor stability and small output, which cannot meet the needs of the market. Contents of the invention

[0003] The purpose of the invention is to overcome the deficiencies in the prior art, and provide a preparation method of 3-bromophenylhydrazine hydrochloride with high purity, large output and good stability.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] A preparation method...

Examples

Embodiment 1

[0018] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0019] ⑴ diazotization

[0020] Add 50g of 3-bromoaniline and 150ml of 37% concentrated hydrochloric acid into a 1L three-necked flask, cool to 2°C with ice salt, add 65g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1 hour.

[0021] ⑵ reduction

[0022] Add 450ml of 37% concentrated hydrochloric acid, 450ml of water and 120g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 20% sodium hydroxide solution until the pH value of the reaction solution is 10, After 1 hour of heat preservation at 5°C, crystals were precipitated, and 24 g of crude 3-bromophenylhydrazine was obtained by filtration.

[0023] ⑶ Purification

[0024] Dissolve 24g of crude 3-bromophenylhydrazine in 480g of water, heat to 60°C to dissolve it completely, the...

Embodiment 2

[0028] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0029] ⑴ diazotization

[0030] Add 200g of 3-bromoaniline and 600ml of 37% concentrated hydrochloric acid into a 5L three-necked flask, cool to 2°C with ice salt, add 270g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0031] ⑵ reduction

[0032] Add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 195g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 25% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 1.5 hours, crystals were precipitated, and 115g of crude 3-bromophenylhydrazine was obtained by filtration.

[0033] ⑶ Purification

[0034] Dissolve 115g of crude 3-bromophenylhydrazine in 2300g of water, heat to 60°C to dissolve it completely, then add a...

Embodiment 3

[0038] A preparation method for 3-bromophenylhydrazine hydrochloride, comprising the following steps:

[0039] ⑴ diazotization

[0040] Add 500g of 3-bromoaniline and 1500ml of 37% concentrated hydrochloric acid into a 10L three-necked flask, cool to 2°C with ice salt, add 650g of 35% sodium nitrite aqueous solution while stirring, and keep the temperature at 2°C for 1.5 hours.

[0041] ⑵ reduction

[0042] Add 730ml of 37% concentrated hydrochloric acid, 730ml of water and 480g of zinc powder to the reaction solution, keep the temperature at 18°C ​​until the reaction is complete, the reaction solution turns off-white, then add 30% sodium hydroxide solution until the pH value of the reaction solution is 10 , kept at 5°C for 2 hours, crystals were precipitated, and 269g of crude 3-bromophenylhydrazine was obtained by filtration.

[0043] ⑶ Purification

[0044] Dissolve 269g of crude 3-bromophenylhydrazine in 5380g of water, heat to 60°C to dissolve it completely, add an app...